He was born in New York City, and educated at Brooklyn College (BA in psychology, 1950; MA in English, 1961). After serving with the United States Maritime Service in 1945-1947, Keyes attended college and then was employed as an associate editor for Marvel Science Fiction (1950-1952), doing much toward improving that magazine during its brief post-WWII period. During the 1950s he also edited/wrote for the Marvel (Timely/Atlas) and EC lines of comic books. He then taught English and creative writing at a succession of schools and colleges, including Wayne State University and Ohio University.

Keyes published the novel The Touch in 1968 [reissued in the United Kingdom as The Contaminated Man in 1977], a half-dozen short stories, and in 1981 the novel The Minds of Billy Milligan (which won the 1985 Kurd Lasswitz Award, the German SF and Fantasy Achievement Award for best foreign novel).

Keyes was one of the editors included in the “All-Star Editor Issue” of Other Worlds Science Stories (June 1952). He also published Understanding Claudia in 1986, a true story of serial murder. Yet “Flowers for Algernon” is the reason he is known today (and famous in SF circles). Although undoubtedly science fiction, the story has been praised as much for its artistic merit as for its science fiction plot. In addition to the award-winning short and long printed forms, the story was made into a full-length play by David Rogers (1969), a TV drama (“The Two Worlds of Charlie Gordon”), and a movie (Charly) and was successful in those media as well.

Interviews with Keyes were published in the June 1997 issue of Locus (“40 Years of Algernon”) and in the March 2002 (#13) issue of Alter Ego (“A Timely Talk with Daniel Keyes”).